The amygdala is a complex medial temporal lobe structure that has been implicated in the mediation of emotion and social behavior. Pathology of the amygdala has been associated with psychiatric conditions including anxiety, panic disorder and social phobia. Social impairment, the core deficit in autism, may also involve dysfunction of the amygdala. The overarching goal of this program of functional neuroanatomical research has been to establish the major intrinsic and extrinsic connections as well as the chemical neuroanatomy of the macaque monkey amygdaloid complex. This information goes some way in defining the neural circuitry mediating social cognition and provides targets for pharmacological modulation of amygdala-based psychopathology. During the current funding period, we have identified virtually all of the cortical inputs to the amygdala. We have also identified new intrinsic connections as we mapped the intra-amygdaloid pathways of the lateral, basal and accessory basal nuclei. We have also conducted detailed immunohistochemical and in situ hybridization studies of the GABA system. In this application we propose to extend our studies of the mature amygdala and to begin research on the developing primate amygdala. We will also initiate studies of the human amygdala both in normal and autistic brains. In the mature monkey brain, we will use electron microscopy to examine the synaptic organization of amygdaloid projections to the neocortex. We will determine whether these projections terminate on principal neurons, interneurons or both. In the neonatal macaque monkey, we will use neural tract tracing techniques to examine the development of amygdaloid projections to the neocortex and neocortical projections to the amygdala. Our goal will be to determine when these connections are established in an adult fashion and how much reorganization occurs during the neonatal period. We will also investigate the distribution of serotonergic innervation of the mature and developing amygdala. Serotonin has been implicated in modulating social function, particularly aggression, but little is known concerning its normal distribution or development in the amygdala. For the first time, we will extend our observation in the monkey to the human amygdala. We hypothesize that the amygdala is dysfunctional in autism and we will attempt to determine whether a neuroanatomical/neurochemical abnormality can be established. We will conduct quantitative, stereological studies on the volume and cell number of the amygdala and its component nuclei and search for pathology of the GABA system, which may be particularly altered in the 30 percent of autistics who also have epilepsy.